DESCRIPTION: Inversions causing hemophilia A in man will be analyzed by extensive analysis of the three A homologous genes on the X chromosome, one of which lies within the factor VIII gene and gives rise to hemophilia A up to 50% of sporadic cases by intrachromosomal homologous recombination with one of the other two A genes. An animal model of hemophilia A will be produced by homologous recombination in mice. This model will be used to study the potential of somatic cell gene therapy and the development of inhibitory antibodies to factor VIII.